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Chemokines Are Associated With Delirium After Cardiac Surgery

¹ Geriatric Research, Education, and Clinical Center, VA Boston Healthcare System, Massachusetts.
² Division of Cardiac Surgery, University of Western Ontario, London, Ontario, Canada.
³ Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington.
⁴ University of Connecticut Center on Aging, University of Connecticut Health Center, Farmington.
⁵ Geriatric Medicine, University of British Columbia, Vancouver, Canada.
Divisions of ⁶ Cardiac Surgery, ⁷ General Medicine and Primary Care, and ⁸ Gerontology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
⁹ Department of Psychiatry and ¹⁰ Division of Aging, Brigham and Women's Hospital, Boston, Massachusetts.

Address correspondence to James L. Rudolph, MD, SM, VABHS Geriatric Research, Education, and Clinical Center, 150 South Huntington Ave (JP-182), Boston, MA 02130. E-mail: jrudolph{at}partners.org

Background. Delirium has been hypothesized to be a central nervous system response to systemic inflammation during a state of blood–brain barrier compromise. The purpose of this study was to compare postoperative changes in groups of inflammatory markers in persons who developed delirium following cardiac surgery and matched controls without delirium.

Methods. Serum samples were drawn from 42 patients undergoing cardiac surgery preoperatively and postoperatively at 6 hours and postoperative day 4. The serum concentrations of 28 inflammatory markers were determined with a microsphere flow cytometer. A priori, inflammatory markers were assigned to five classes of cytokines. A class z score was calculated by averaging the standardized, normalized levels of the markers in each class. Beginning on postoperative day 2, patients underwent a daily delirium assessment.

Results. Twelve patients with delirium were matched by surgical duration, age, and baseline cognition to 12 patients without delirium. At the 6-hour time point, patients who went on to develop delirium had higher increases of chemokines compared to matched controls (class z score 0.3 ± 1.0, p <.05). Among the five classes of cytokines, there were no other significant differences between patients with or without delirium at either the 6 hour or postoperative day 4 assessments.

Conclusion. After cardiac surgery, chemokine levels were elevated in patients who developed delirium in the early postoperative period. Because chemokines are capable of disrupting blood–brain barrier integrity in vitro, future studies are needed to define the relationship of these inflammatory mediators to delirium pathogenesis.

Key Words: Inflammation • Delirium • Cardiac surgery • Chemokines • Cytokines

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